Doublecortin expression in prostate adenocarcinoma and neuroendocrine tumors.

Abstract: Introduction Recent work using prostate cancer mouse models implicated doublecortin (DCX)-expressing neural progenitor cells in prostate adenocarcinoma, reporting a strong association between DCX expression and histologic grade and clinical outcome. We sought to evaluate the relationship between DCX expression and these variables in human prostate cancer. Methods and Materials DCX expression was measured in transcriptome-wide microarray data from 18,501 patients with localized prostate cancer and 290 patients with metastatic castration-resistant prostate cancer (mCRPC), and compared across disease states, histologic grades, and clinical outcomes. Biochemical recurrence-free survival (BRFS), metastasis-free survival (MFS) and overall survival (OS) were analyzed using Cox-proportional hazards. Results DCX expression was not significantly different between normal prostate (n=29), primary prostate cancer (n=131), or metastases (n=19), and did not increase with grade group in a large cohort of RP samples (n=17,967). Those with DCX expression above and below the median did not have significant differences in BRFS (HR 1.15 [0.88-1.49], p=0.31), MFS (HR 1.2 [0.84-1.7], p=0.3) or OS (HR 1.15 [0.7-1.84], p =0.56). In a cohort of untreated prostate cancer, DCX expression was higher in neuroendocrine tumors (n=10) compared to grade group 5 prostate adenocarcinoma (n=110) (p=0.007). Similarly, in two cohorts with mCRPC (n=290), DCX expression was higher in lesions with neuroendocrine features than adenocarcinoma (p Conclusions Contrary to recent data using mouse models, DCX expression did not differ by disease state or outcome, and did not increase with grade in a large dataset of human patients with prostate adenocarcinoma. However, DCX expression appeared to correlate with neuroendocrine histology, a subgroup that can arise de novo or in the castrate-resistant setting. Further work is needed to define the role of DCX and its clinical significance in prostate cancer.